Effect of Live Attenuated Influenza Vaccine on Pneumococcal Carriage

Rylance, J.; de Steenhuijsen Piters, W. A.; Pojar, S.; Nikolaou, E.; German, E.; Mitsi, E.; Jochems, S.; Carniel, B.; Solorzano, C.; Reine, J.; Gritzfeld, J.; Chu, M. L. J.; Arp, K.; Hyder-Wright, A. D.; Hill, H.; Hales, C.; Robinson, R.; Lowe, C.; Adler, H.; Zaidi, S.; Connor, V.; Lazarove, L.; Piddock, K.; Wheeler, I.; Smith, E.; Morton, B.; Blakey, J.; Burhan, H.; Koukounari, A.; Wang, D.; Mina, M. J.; Gordon, S. B.; Bogaert, D.; French, N.; Ferreira, D. M.

doi:10.1101/343319

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bioRxiv · 10.1101/343319

Effect of Live Attenuated Influenza Vaccine on Pneumococcal Carriage

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Abstract

The widely used nasally-administered Live Attenuated Influenza Vaccine (LAIV) alters the dynamics of naturally occurring nasopharyngeal carriage of Streptococcus pneumoniae in animal models. Using a human experimental model (serotype 6B) we tested two hypotheses: 1) LAIV increased the density of S. pneumoniae in those already colonised; 2) LAIV administration promoted colonisation. Randomised, blinded administration of LAIV or nasal placebo either preceded bacterial inoculation or followed it, separated by a 3-day interval. The presence and density of S. pneumoniae was determined from nasal washes by bacterial culture and PCR. Overall acquisition for bacterial carriage were not altered by prior LAIV administration vs. controls (25/55 [45.5%] vs 24/62 [38.7%] respectively, p=0.46). Transient increase in acquisition was detected in LAIV recipients at day 2 (33/55 [60.0%] vs 25/62 [40.3%] in controls, p=0.03). Bacterial carriage densities were increased approximately 10-fold by day 9 in the LAIV recipients (2.82 vs 1.81 log10 titers, p=0.03). When immunisation followed bacterial acquisition (n=163), LAIV did not change area under the bacterial density-time curve (AUC) at day 14 by conventional microbiology (primary endpoint), but significantly reduced AUC to day 27 by PCR (p=0.03). These studies suggest that LAIV may transiently increase nasopharyngeal density of S. pneumoniae. Transmission effects should therefore be considered in the timing design of vaccine schedules.\n\nTrial registrationThe study was registered on EudraCT (2014-004634-26)\n\nFundingThe study was funded by the Bill and Melinda Gates Foundation and the UK Medical Research Council.

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Rylance, J., de Steenhuijsen Piters, W. A., Pojar, S., Nikolaou, E., German, E., Mitsi, E., Jochems, S., Carniel, B., Solorzano, C., Reine, J., Gritzfeld, J., Chu, M. L. J., Arp, K., Hyder-Wright, A. D., Hill, H., Hales, C., Robinson, R., Lowe, C., Adler, H., Zaidi, S., Connor, V., Lazarove, L., Piddock, K., Wheeler, I., Smith, E., Morton, B., Blakey, J., Burhan, H., Koukounari, A., Wang, D., Mina, M. J., Gordon, S. B., Bogaert, D., French, N., Ferreira, D. M.. 2018-06-14. Effect of Live Attenuated Influenza Vaccine on Pneumococcal Carriage. https://doi.org/10.1101/343319

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